anaesthesia considerations and implications during oncologic and non-oncologic surgery in cancer...

Anaesthesia considerations and Implications during

Oncologic and Non-Oncologic surgery in Cancer patients

Theme Symposium

Anaesthesia considerations and implications duringoncologic and non-oncologic surgery in cancer patients

Sukhminder Jit Singh Bajwa a,*, Ashish Kulshrestha b

aAssociate Professor, Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur,

Punjab, IndiabAssistant Professor, Gian Sagar Medical College and Hospital, Banur, Patiala, Punjab, India

a r t i c l e i n f o

Article history:

Received 24 June 2012

Accepted 13 February 2013

Available online xxx

Keywords:

Malignancy

Chemotherapeutic agents

Anaesthesia

Surgery

a b s t r a c t

Cancer has been the leading cause of mortality in both developed and developing coun-

tries. With the advancement in chemotherapeutic agents, the quality and lifespan of pa-

tients with advanced malignancies has improved. These patients often come to hospitals

for various types of elective and emergency surgeries. The attending anaesthesiologist

faces a daunting task while managing these patients as there can be gross physiological

derangements in most of the organ systems. A careful and thorough preoperative

assessment, optimisation of physiological milieu, vigilant intraoperative monitoring,

anticipation of potential complications and postoperative pain control is essential for

reducing perioperative mortality and morbidity in these patients. The toxicity of chemo-

therapeutic agents and potential drug interactions with selected anaesthetic drugs are of

prime concern while anaesthetizing such patients. The build-up of nutrition in these

patients is essential during preoperative period and should be continued during post-

operative period also.

Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

Malignancy has become one of the leading causes of death

especially in developed world and even in developing coun-

tries; its incidence has increased tremendously over the last

few decades. In 2008, it was found that about 12.7 million pa-

tientswerediagnosedof someformofmalignanciesworldwide

out of which about 7.6 million died of the malignancy itself or

its associated complications.1 Malignancy as a group accounts

forabout13%ofalldeathsperyearwith themostcommonsites

being lung/bronchus, colorectal, breast and prostate.2 The

most common types of malignancies found in children are

leukaemia (34%), brain tumours (23%) and lymphoma (12%).3

With the advent of newer and advanced chemotherapeutic

agents, survival and lifespan of these patients has witnessed a

tremendous increase. As a result, large number of these cancer

patients during post cancer treatment presents either for sur-

gical intervention for the primary tumour excision or emer-

gency intervention for their various ill effects. Due tomultitude

of effects of malignancy on various systems in the body and

effects of chemotherapeutic agents, thesepatients pose a great

challenge to the attending anaesthesiologist.4

* Corresponding author. House No-27-A, Ratan Nagar, Tripuri, Patiala, Punjab 147001, India. Tel.: þ91 (0) 9915025828, þ91 1752352182.E-mail addresses: [email protected], [email protected] (S.J.S. Bajwa).

Available online at www.sciencedirect.com

journal homepage: www.elsevier .com/locate/apme

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Please cite this article in press as: Bajwa SJS, Kulshrestha A, Anaesthesia considerations and implications during oncologic andnon-oncologic surgery in cancer patients, Apollo Medicine (2013), http://dx.doi.org/10.1016/j.apme.2013.02.004

0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apme.2013.02.004

2. Effects of tumour on the body

2.1. Local effects of tumours

Tumours of head, neck and pose significant problems in

maintenance of airway especially after induction of anaes-

thesia due to their extrinsic compressive effects ormay be due

to presence of intrinsic tumour.5 Preoperatively, radiographic

examination of soft tissues of neck and computed tomogra-

phy of neck is mandatory in these patients for careful preop-

erative planning for securing an unobstructed airway.

Planned awake fibreoptic guided intubation may be required

in tumours with extrinsic compression on airway and a pre-

operative tracheostomy may be required in patients with an

anticipated difficult fibreoptic intubation due to presence of

large vascular tumour inside the airways. Postoperatively

these patients can be at risk of airway compromise due to

oedema of larynx and neck structures which may warrant

continuing the mechanical ventilation in these patients till

the airway oedema subsides.

Superior vena cava syndromemay develop in primary lung

malignancy due to obstruction of venous return from the head

and neck by the tumours. It may be an acute or subacute

process and results in facial oedema, plethora, dilatation of

veins of chest wall and neck, headache, conjunctival oedema,

respiratory difficulty, visual disturbances and altered level of

consciousness. Diagnosis is usually clinical or by non-invasive

venous studies. Therapy includes administration of throm-

bolytic agents and/or emergent radiotherapy in patients with

airway compromise.6

Pericardial effusion and cardiac tamponade are rare due

to the primary tumours of pericardium but are usually due to

metastasis to the pericardium. Acute accumulation of as

little as 100 ml of fluid in pericardial cavity can lead to

tamponade and cardiovascular collapse while chronic accu-

mulation of large volumes of fluid can be accommodated

inside the pericardial cavity due to the stretching of the

pericardium. Echocardiography is the investigation of choice

and can detect as little as 15 ml of pericardial fluid.7 Treat-

ment depends on the degree of haemodynamic compromise

and can involve pericardiocentesis or pericardiectomy

depending on the aetiology of diffusion and its likely

recurrence.

2.2. Systemic effects of tumour

� Pain is a common symptom in patients with malignant tu-

mours with an incidence of 25% in newly diagnosed malig-

nancies and upto 75% in advanced disease.8 It may be due to

involvement of somatic nerves by tumour itself or by the

systemic metastasis. These patients can present for various

procedures for relief of chronic pain like nerve blocks, gan-

glion blocks etc.

� Majority of patients with advanced malignancy present

with cachexia which is characterised by significant weight

loss, anorexia, weakness, poor performance and impaired

immune function.9 These cachectic patients pose signifi-

cant challenges to the attending anaesthesiologist due to

their disturbed homoeostasis

� Renal failure can develop in cancer patients by both pre-

renal as well as intrinsic renal mechanisms. However, pre-

existing renal and renal endocrine disorders can be more

challenging in such patients.10 Pre-renal causes include

dehydration due to cachexia or poor oral intake and

intrinsic renal causes includes sepsis syndrome or use of

nephrotoxic chemotherapeutic agents. Post-renal failure

also is likely in obstruction of renal outflow tract by pelvic

tumours, prostate or cervical malignancies.11

� Infection is a common and unfavourable effect of malig-

nancy which is mainly contributed by depressed immuno-

logic function due to neutropenia. It may occur due to

malignancy interfering with bone marrow functions or may

be due to drug induced myelosuppression. These nosoco-

mial infections increase hospital stay and the cost to

patient.12

� A characteristic constellation of systemic symptoms termed

as ‘paraneoplastic syndrome’ can occur due to secretion of

various hormones from the primary tumour into the circu-

lation which causes various metabolic abnormalities like

myasthenic syndrome in thymoma, syndrome of inade-

quate secretion of antidiuretic hormone (SIADH) seen in

small cell carcinoma bronchus and so on.13

� Electrolyte abnormalities usually develop in malignancy,

the commonest being hypercalcaemia which develops in

about 10% of all malignancies and is due to bony metastasis

causing bone resorption. Other abnormality seen is hypo-

natremia which may develop due to SIADH or due to

impaired ability to produce dilute urine.

� Tumour lysis syndrome is a constellation of symptoms that

is associated with cytotoxic therapy ofmalignancy resulting

in various metabolic derangements like hyperuricemia,

hypocalcemia, hyperkalemia, hyperphosphatemia and

uraemia leading to acute renal failure. It is associated with

leukaemia, small cell carcinoma lung, testicular and breast

cancer.14

2.3. Haematological effects

The haematologic effects of malignancy are due to a primary

malignancy of bone marrow (leukaemia), metastasis or mye-

losuppression due to chemotherapeutic agents. The major

haematologic effects seen are:

� Anaemia is a common finding and suggests chronicity of the

disease with significantly low erythropoietin levels due to

direct suppression of erythropoietin secreting cells by the

malignancy or due to suppressive effects of radiotherapy

and chemotherapy.15

� Leukopenia is most often associated with the chemothera-

peutic treatment of solid tumours and is directly related to

the incidence of systemic infections.16

� Thrombocytopenia occurring in malignancy is usually

due to effects of chemotherapy and radiotherapy on bone

marrow function and may also be due to splenic

sequestration of platelets because of enlarged spleen.

Thrombosis can also occur in about 2e10% of cases of

cancer and may be the first indication of an occult

malignancy.17



2.4. Effects of anticancer treatment

The treatment of cancer involves selective destruction of

malignant cells by both radiation therapy and by chemo-

therapeutic agents directed against malignant cells. This

anticancer therapy has various negative effects on bodywhich

may cause debilitating effects on normal body homoeostasis.

1. Effects of radiation therapy: Radiations are used in specific

tumours to achieve complete cure and in some tumours to

achieve palliation. The ill effects of radiation therapy

depend upon the intensity of radiation used.16 The various

effects of radiation therapy are18,19:

� Direct effect of radiation can cause epidermal desqua-

mation and pigmentation which can lead to contractures

of irradiated area.

� Acute radiation enteritis can result due to radiation

inducedmucositis and is often self-limiting but long term

effects can result in strictures, obstruction, perforation

and fistula formation, which may require emergency

intervention.

� Acute radiation pneumonitis can develop in lungs

resulting in reduced pulmonary compliance and dysp-

noea which can lead to pulmonary fibrosis in long term.

� The nervous system is usually least affected and radia-

tion induced peripheral neuropathy is seen with mixed

sensory and motor deficits.

� Radiation nephropathy can result in proteinuria and hy-

pertension and treatment with angiotensin converting

enzyme inhibitors (ACEI) can reduce its severity.

� The radiation induced cardiac injury usually manifest as

mild pericarditis and pericardial effusion after 6 months

of therapy.

� The hepatic injury can occur as an acute reaction within

2e6 weeks of initiation of therapy with hepatic enlarge-

ment and portal hypertension and abnormal liver func-

tion tests whereas a chronic form occurring after 6

months usually results in progressive cirrhosis.

� Radiation therapy causes swelling and oedema of soft

tissues of head and neck which can later result in fibrosis

posing difficulties in intubation of these patients.

2. Effects of chemotherapy: With recent advancement in

chemotherapeutic agents, more number of cancer patients

are being treated with these agents. Apart from their

cytotoxic effects on malignant cells, they also have toxic

effects on normal body cells which cause their side-

effects.20,21 The various chemotherapeutic agents with

their side-effects are summarised in Table 122:

3. Anaesthetic considerations in patientswith cancer

The patients with malignancy can present with myriad of

physiological alterations in body systems which place these

patients at an extra risk during the perioperative period as

compared to the normal population. These patients can pre-

sent for various surgeries for resection of primary tumour,

diagnostic procedures for unknown primary or emergency

surgery for complication of malignancy. The risks increase to

a greater extent if such patients present with untreated co-

morbid diseases.23 The anaesthetic management of these

patients require a sound knowledge of the various physio-

logical alterations and should involve:

3.1. Preoperative assessment

A thorough preoperative assessment is mandatory to know

the physical status of the patient, the stage of malignancy and

the risk involved with the surgery.

� The assessment of the nutritional status of the patient is

essential as these patients are often poorly nourished

because of themalignancy. The build-up of nutritional state

is mandatory for a positive postoperative outcome and can

be achieved with hyperalimentation or parenteral nutrition.

� Due to the physiological alterations in patients with malig-

nancy, these often have electrolyte abnormalities which

should be corrected preoperatively for better intra and

postoperative haemodynamic stability.

� Assessment of cardiopulmonary reserve is very essential as

the cardiovascular system is often involved by the primary

malignancy, metastatic disease or by the radiotherapy or

chemotherapeutic agents. Any involvement of cardiovas-

cular system should prompt to undergo echocardiography

and exercise stress testing and further invasive testing with

angiography should be considered in specific conditions.24

� Several endocrine abnormalities exist in these patients

including diabetes mellitus, diabetes insipidus, hypopitu-

itarism, thyroid dysfunction, adrenal cortical andmedullary

Table 1 e Showing various chemotherapeutic agents and their associated side-effects.

Class Drugs Side-effects

Alkylating agents Busulfan, Chlorambucil, Cyclophosphamide, Melphalan,

Isofosfamide

Myelosuppression, uric acid nephropathy, nausea &

vomiting, hemorrhagic cystitis, carcinogenic, SIADH

Antimetabolites Methotrexate, Fluorouracil, Gemcitabine,

Mercaptopurine

Myelosuppression, dermatitis, alopecia, pulmonary

fibrosis, nephrotoxicity,

Vinca alkaloids Vincristine, Vinblastine, Paclitaxel, Etoposide, Docetaxel Autonomic & peripheral neuropathy, myelosuppression,

dermatitis, cardiotoxicity

Antibiotics Bleomycin, Doxorubicin, Daunorubicin, Mitoxantrone Pulmonary fibrosis, cardiotoxicity, myelosuppression,

dermatitis

Hormones Tamoxifen, Letrozole, Flutamide, Oestrogen Myelosuppression, coagulation abnormalities,

hemorrhagic cystitis

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dysfunction, calcium disorders etc.25e28 Preoperative review

and management of all these condition is essential for

preventing intra and postoperative complications. Such

patients may require intensive care monitoring during

postop period.

� Patients having co-morbid psychiatric and psychologic dis-

orders are difficult to treat. The preoperative evaluation is

extremely challenging in such patients as the elicitation of

proper history and relevant clinical examination is difficult

as these patients exhibit a different degree of co-operation

during such evaluation.29

� A deranged haemogram is often encountered in these pa-

tients and any correctable causes of such abnormalities

should be identified and appropriately treated for a better

postoperative outcome like stem cell stimulation therapy

and correcting the coagulation defects.30

� As a rule, all patients with malignancy should have exten-

sive preoperative testing which should include complete

haemogram, coagulation profile, liver function test, renal

function test, electrolytes, 12 lead electrocardiogram and

chest radiograph.

� Airway assessment is of utmost importance to an anaes-

thesiologist especially in head and neck malignancies to

anticipate any intubation difficulties and to develop a plan

to overcome such difficulties.

3.2. Intraoperative management

Intraoperative management of these patients is as important

as the preoperative assessment as these patients are prone to

develop serious intraoperative cardiovascular complications

due to their disturbed homoeostasis:

� These patients should be monitored with the standard

intraoperative monitors including non-invasive blood

pressure, electrocardiogram, pulse oximeter, end-tidal car-

bon dioxide monitor, temperature probe and urine output.

Invasive monitoring should be used wherever the clinical

condition of the patient mandates.

� Intraoperative temperature monitoring is essential to

maintain the temperature as these patients are prone to

develop hypothermia. Forced convective air warming de-

vices are beneficial inmaintaining normothermia to prevent

ill effects of hypothermia in the postoperative period.31

Shivering is a very unpleasant phenomenon in post-

operative patients. Numerous drugs have been used to

control the incidence of postoperative shivering with a

varying level of success. Dexmedetomidine is the newer

addition to the anaesthesiologist’s armamentarium for

control of this postoperative menace.32

� As mentioned earlier, airway maintenance in patients with

head and neck malignancies is essential and should be

planned preoperatively. The decision of awake fibreoptic

guided intubation or elective tracheostomy should be based

on clinical judgement of the anaesthesiologist.

� Positioning of the patient is a very important but often

neglected part in the intraoperative management of these

patients. There are different types of positions which are

employed by the surgeons depending upon type of surgery

like supine, lateral decubitus, prone etc. The common pre-

cautionswhichshouldbe taken ineachof thesepositionsare:

- proper padding of all the pressure points,

- avoidance of excessive stretching of the nerve plexuses

especially in upper limbs,

- proper positioning of eyes in prone position to prevent

postoperative blindness and

- avoidance of compression on abdomen in prone posi-

tion to facilitate proper ventilation.

� Blood component therapy in these patients should be

guided by clinical judgement. Risk of transmission of

infection in these immunocompromised patients should be

weighed with the benefits of blood transfusion. A value of

6e8 g/dl for haemoglobin is considered a threshold for pa-

tients without any preoperative risk factors and 10e11 g/dl

for those with significant risk factors.33

� Blood conservation strategies may be employed to prevent

excessive intraoperative blood loss like preoperative em-

bolisation of highly vascular tumours and metastases.

Intraoperative cell salvage have been controversial as it can

increase the risk of spreading the cancerous cells systemi-

cally, however use of filtration and irradiation have found

some use in reducing tumour load of the salvaged blood.34

Use of antifibrinolytics have been studied recently and

have been found to significantly reduce the intraoperative

blood loss with reduced need for allogenic blood trans-

fusions and also no significant increased incidence of

venous thrombosis have been found.35

� Benzodiazepines have been shown to alter the immuno-

logical response to stress of surgery by reduction in cyto-

kines release and thus may be beneficial in these patients.36

� General anaesthesia have been found to be immunomodula-

tory in these patients by interfering with functions of immu-

nological cells like natural killer cells (NK), macrophages and

can increase the mortality associated with postoperative

wound healing.37 However, wherever general anaesthesia is

necessary, efforts should bedone to administerminimal dose

of anaesthetics by addition of adjuvants like dexmedetomi-

dine which definitely decreases the dose of analgesics and

anaesthetics.38 Total intravenous anaesthesia is better alter-

native for a rapid and smooth recovery from anaesthesia.39

� Regional anaesthesia alone or combined with general

anaesthesia have been found to not only cause reduction of

stress response to surgical stress but also to reduce the

occurrence of metastasis in advanced malignancies.40e42

Administration of regional anaesthesia should aim at

administering minimal dose of local anaesthetics and this

can be achieved with addition of adjuvants like dexmede-

tomidine, fentanyl, clonidine and so on wherever

feasible.43e45 However, regional anaesthesia becomes chal-

lenging in patients with suspected metastasis to the spine.

Elicitation of paraesthesia during administration of epidural

regional anaesthesia should prompt one to discard this

technique and should resort to general anaesthesia.46

3.3. Postoperative management

A careful postoperative monitoring of these patients in a high

dependency unit is desirable especially in patients with



significant risk factors. In few patients, the postoperative

intensive care becomes essential and such patients have to be

shifted to ICU for further management. Prognosis and costs

involved in the treatment of such patients should be thor-

oughly explained to the patient’s relative in their own

vernacular.47 Alleviation of acute surgical pain is of utmost

importance in the postoperative period with advanced ma-

lignancies to reduce the stress response and to aid in proper

wound healing. These patients are often on long term oral

opioids which should be replaced with parenteral formula-

tions and the dose carefully titrated to the desired effect with

an additional 30% of the dose added for the acute post-

operative pain over and above the usual dose of opioids.48 The

nutritional aspects cannot be ignored at all in these patients

especially in preoperative malnourished and aged patients.

The nutritional supplements should be continued during the

postoperative period whether they are in ward, high de-

pendency units or intensive care units.49

3.4. Thromboprophylaxis

Venous thromboembolism is a serious postoperative compli-

cationespecially inpatientswithmalignancywithan incidence

of 45e69% without any prophylaxis. Various mechanical and

pharmacological methods can be employed and the incidence

of deep vein thrombosis can be reduced to 4%.50,51 The various

pharmacological methods are use of warfarin, low-dose hepa-

rin, low molecular weight heparin and aspirin. An important

implicationofuseof thromboprophylaxis for anaesthesiologist

is when epidural catheter is in place, so that the removal of the

catheter should take place at an appropriate time period to

prevent development of any epidural haematoma.

4. Conclusion

In conclusion, anaesthesia for patients with cancer pose sig-

nificant challenges due to physiological alterations caused by

malignancy itself, due to distant metastasis and also due to

endocrine changes brought about by the tumour. A thorough

preoperative assessment with correction of nutritional status

and electrolyte abnormalities, careful intraoperative planning

and monitoring and intensive postoperative monitoring and

relief of acute postoperative pain, is essential for a positive

outcome of the patient. The effect of anaesthesia on malig-

nancy is a matter of debate and should be consolidated by

further randomised controlled studies.

Conflicts of interest

All authors have none to declare.

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